Combining Radiation- with Immunotherapy in Prostate Cancer: Influence of Radiation on T Cells

Radiation of tumor cells can lead to the selection and outgrowth of tumor escape variants. As radioresistant tumor cells are still sensitive to retargeting of T cells, it appears promising to combine radio- with immunotherapy keeping in mind that the radiation of tumors favors the local conditions for immunotherapy. However, radiation of solid tumors will not only hit the tumor cells but also the infiltrated immune cells. Therefore, we wanted to learn how radiation influences the functionality of T cells with respect to retargeting to tumor cells via a conventional bispecific T cell engager (BiTE) and our previously described modular BiTE format UNImAb. T cells were irradiated between 2 and 50 Gy. Low dose radiation of T cells up to about 20 Gy caused an increased release of the cytokines IL-2, TNF and interferon-γ and an improved capability to kill target cells. Although radiation with 50 Gy strongly reduced the function of the T cells, it did not completely abrogate the functionality of the T cells.     

Non-Functionalized Gold Nanoparticles Inhibit Human Papillomavirus (HPV) Infection

The spontaneous interaction between human papillomavirus type 16 (HPV16) L1 virus-like particles (VLPs) and non-functionalized gold nanoparticles (nfGNPs) interferes with the nfGNPs’ salt-induced aggregation, inhibiting the red–blue color shift in the presence of NaCl. Electron microscopy and competition studies showed that color-shift inhibition is a consequence of direct nfGNP–VLP interaction and, thus, may produce a negative impact on the virus entry cell process. Here, an in vitro infection system based on the HPV16 pseudovirus (PsV) was used to stimulate the natural infection process in vitro. PsVs carry a pseudogenome with a reporter gene, resulting in a fluorescent signal when PsVs infect a cell, allowing quantification of the viral infection process. Aggregation assays showed that nfGNP-treated PsVs also inhibit color shift in the presence of NaCl. High-resolution microscopy confirmed nfGNP–PsV complex formation. In addition, PsVs can interact with silver nanoparticles, suggesting a generalized interaction of metallic nanoparticles with HPV16 capsids. The treatment of PsVs with nfGNPs produced viral infection inhibition at a higher level than heparin, the canonical inhibitor of HPV infection. Thus, nfGNPs can efficiently interfere with the HPV16 cell entry process and may represent a potential active component in prophylactic formulations to reduce the risk of HPV infection.     

Systemic Dietary Hesperidin Modulation of Osteoclastogenesis,Bone Homeostasis and Periodontal Disease in Mice

This study aimed to evaluate the effects of hesperidin (HE) on in vitro osteoclastogenesis and dietary supplementation on mouse periodontal disease and femoral bone phenotype. RAW 264.7 cells were stimulated with RANKL in the presence or absence of HE (1, 100 or 500 µM) for 5 days, and evaluated by TRAP, TUNEL and Western Blot (WB) analyses. In vivo, C57BL/6 mice were given HE via oral gavage (125, 250 and 500 mg/kg) for 4 weeks. A sterile silk ligature was placed between the first and second right maxillary molars for 10 days and microcomputed tomography (μCT), histopathological and immunohistochemical evaluation were performed. Femoral bones subjected or not to dietary HE (500 mg/kg) for 6 and 12 weeks were evaluated using μCT. In vitro, HE 500 µM reduced formation of RANKL-stimulated TRAP-positive(+) multinucleated cells (500 µM) as well as c-Fos and NFATc1 protein expression (p < 0.05), markers of osteoclasts. In vivo, dietary HE 500 mg/kg increased the alveolar bone resorption in ligated teeth (p < 0.05) and resulted in a significant increase in TRAP+ cells (p < 0.05). Gingival inflammatory infiltrate was greater in the HE 500 mg/kg group even in the absence of ligature. In femurs, HE 500 mg/kg protected trabecular and cortical bone mass at 6 weeks of treatment. In conclusion, HE impaired in vitro osteoclastogenesis, but on the contrary, oral administration of a high concentration of dietary HE increased osteoclast numbers and promoted inflammation-induced alveolar bone loss. However, HE at 500 mg/kg can promote a bone-sparing effect on skeletal bone under physiological conditions.     

Role of Micronutrients and Gut Microbiota-Derived Metabolites in COVID-19 Recovery

A balanced and varied diet provides diverse beneficial effects on health, such as adequate micronutrient availability and a gut microbiome in homeostasis. Besides their participation in biochemical processes as cofactors and coenzymes, vitamins and minerals have an immunoregulatory function; meanwhile, gut microbiota and its metabolites coordinate directly and indirectly the cell response through the interaction with the host receptors. Malnourishment is a crucial risk factor for several pathologies, and its involvement during the Coronavirus Disease 2019 pandemic has been reported. This pandemic has caused a significant decline in the worldwide population, especially those with chronic diseases, reduced physical activity, and elder age. Diet and gut microbiota composition are probable causes for this susceptibility, and its supplementation can play a role in reestablishing microbial homeostasis and improving immunity response against Coronavirus Disease 2019 infection and recovery. This study reviews the role of micronutrients and microbiomes in the risk of infection, the severity of disease, and the Coronavirus Disease 2019 sequelae.     

An Overview of PRR- and NLR-Mediated Immunities: Conserved Signaling Components across the Plant Kingdom That Communicate Both Pathways

Cell-surface-localized pattern recognition receptors (PRRs) and intracellular nucleotide-binding domain and leucine-rich repeat receptors (NLRs) are plant immune proteins that trigger an orchestrated downstream signaling in response to molecules of microbial origin or host plant origin. Historically, PRRs have been associated with pattern-triggered immunity (PTI), whereas NLRs have been involved with effector-triggered immunity (ETI). However, recent studies reveal that such binary distinction is far from being applicable to the real world. Although the perception of plant pathogens and the final mounting response are achieved by different means, central hubs involved in signaling are shared between PTI and ETI, blurring the zig-zag model of plant immunity. In this review, we not only summarize our current understanding of PRR- and NLR-mediated immunities in plants, but also highlight those signaling components that are evolutionarily conserved across the plant kingdom. Altogether, we attempt to offer an overview of how plants mediate and integrate the induction of the defense responses that comprise PTI and ETI, emphasizing the need for more evolutionary molecular plant–microbe interactions (EvoMPMI) studies that will pave the way to a better understanding of the emergence of the core molecular machinery involved in the so-called evolutionary arms race between plants and microbes.     

A time fractional model to represent rainfall process简

This paper deals with a stochastic representation of the rainfall process.The analysis of a rainfall time series shows that cumulative representation of a rainfall time series can be modeled as a non-Gaussian random walk with a log-normal jump distribution and a time-waiting distribution following a tempered α-stable probability law.Based on the random walk model,a fractional Fokker-Planck equation(FFPE) with tempered α-stable waiting times was obtained.Through the comparison of observed data and simulated results from the random walk model and FFPE model with tempered α-stable waiting times,it can be concluded that the behavior of the rainfall process is globally reproduced,and the FFPE model with tempered α-stable waiting times is more efficient in reproducing the observed behavior.     

Progress on Electrospun Composite Fibers Incorporating Bioactive Glass: An Overview

Electrospinning is a promising approach for the development of fibrous tissue engineering (TE) scaffolds suitable for hard and soft tissues. Apart from physicomechanical properties, electrospun fibers are required to incorporate bioactive cues to control cellular functions, including facilitating biomineralization and osteogenic differentiation in case of bone TE, as well as vascularization, to support successful tissue regeneration. In recent years, bioactive glass (BG) addition to electrospun biopolymer fibers has shown promising results in enhancing the properties of fibers, including the improvement of biological performance. In this article, a comprehensive overview of BG-containing electrospun polymer composite fibers is presented, identifying the parameters that affect the mechanical properties as well as the biological response in vivo and in vitro. Subsequently, the effects of BG addition on the properties of the scaffolds are discussed. Recent developments in the fields of bone regeneration, wound healing, and drug delivery using BG-containing electrospun fibrous scaffolds are described in detail. Essential aspects related to BG-polymer composite fibers for translational research in TE are highlighted for future research in this field.     

Dry surface biofilms in the food processing industry: An overview on surface characteristics,adhesion and biofilm formation,detection of biofilms,and dry sanitization methods

Bacterial biofilm formation in low moisture food processing (LMF) plants is related to matters of food safety, production efficiency, economic loss, and reduced consumer trust. Dry surfaces may appear dry to the naked eye, however, it is common to find a coverage of thin liquid films and microdroplets, known as microscopic surface wetness (MSW). The MSW may favor dry surface biofilm (DSB) formation. DSB formation is similar in other industries, it occurs through the processes of adhesion, production of extracellular polymeric substances, development of microcolonies and maturation, it is mediated by a quorum sensing (QS) system and is followed by dispersal, leading to disaggregation. Species that survive on dry surfaces develop tolerance to different stresses. DSB are recalcitrant and contribute to higher resistance to sanitation, becoming potential sources of contamination, related to the spoilage of processed products and foodborne disease outbreaks. In LMF industries, sanitization is performed using physical methods without the presence of water. Although alternative dry sanitizing methods can be efficiently used, additional studies are still required to develop and assess the effect of emerging technologies, and to propose possible combinations with traditional methods to enhance their effects on the sanitization process. Overall, more information about the different technologies can help to find the most appropriate method/s, contributing to the development of new sanitization protocols. Thus, this review aimed to identify the main characteristics and challenges of biofilm management in low moisture food industries, and summarizes the mechanisms of action of different dry sanitizing methods (alcohol, hot air, UV-C light, pulsed light, gaseous ozone, and cold plasma) and their effects on microbial metabolism.     

Mass spectrometry-based approaches to assess the botanical authenticity of dietary supplements

Dietary supplements are legally considered foods despite frequently including medicinal plants as ingredients. Currently, the consumption of herbal dietary supplements, also known as plant food supplements (PFS), is increasing worldwide and some raw botanicals, highly demanded due to their popularity, extensive use, and/or well-established pharmacological effects, have been attaining high prices in the international markets. Therefore, botanical adulteration for profit increase can occur along the whole PFS industry chain, from raw botanicals to plant extracts, until final PFS. Besides the substitution of high-value species, unintentional mislabeling can happen in morphologically similar species. Both cases represent a health risk for consumers, prompting the development of numerous works to access botanical adulterations in PFS. Among different approaches proposed for this purpose, mass spectrometry (MS)-based techniques have often been reported as the most promising, particularly when hyphenated with chromatographic techniques. Thus, this review aims at describing an overview of the developments in this field, focusing on the applications of MS-based techniques to targeted and untargeted analysis to detect botanical adulterations in plant materials, extracts, and PFS.